1. Field of the Invention
The present invention is a novel process and novel intermediates to prepare [R-(R*,R*)]-N-[3-[1-[5,6-dihydro-4-hydroxy-2-oxo-6-(2-phenylethyl)-6-propy l-2H-pyran-3-yl]propyl]phenyl]-5-(trifluoromethyl)-2-pyridinesulfonamide (XIX) which is a protease inhibitor useful in treating humans infected with the HIV virus.
2. Description of the Related Art
[R-(R*,R*)]-N-[3-[1-[5,6-Dihydro-4-hydroxy-2-oxo-6-(2-phenylethyl)-6-propyl -2H-pyran-3-yl]propyl]phenyl]-5-(trifluoromethyl)-2-pyridinesulfonamide (XIX) can be produced by the process set forth in International Publications WO95/30670 and WO94/11361.
J. Med. Chem., 39(22), 4349 (1996) discloses the cyclic ester (VI) but in the racemic form. This document also discloses the transformation of the cyclic ester (VI) to the protease inhibitor (XIX) but by a different synthetic pathway.
J. Am. Chem. Soc., 111, 3627 (1997) discloses the amino compound (XVIII).
Tetrahedron Letters, 34(2), 277-280 (1993) discloses a method for the conversion of a .beta.-hydroxycarbonyl compound to a ring similar to that of formulas (VI) and (CVI). The .beta.-hydroxycarbonyl compound in the prior art is a secondary alcohol and that in the present invention is a tertiary alcohol. In addition, the processes are completely different with the process of Tetrahedron Letters not being operable on the tertiary alcohols (IV) and (CIV) of the present invention.
J. Med. Chem., 39(23), 4630-4642 (1996) discloses a method to make compounds similar to that of formulas (VI) and (CVI) but in racemic form from starting materials different from the present invention by an unrelated method.
International Publication WO95/14012 claims a cyclic compound similar to the cyclic compounds (VI), (XVII) and (XXV) of the present invention but in racemic form. The process of the present invention produces these compounds in optically pure form.
International Publication WO94/11361 discloses the cyclic ester (VI) but in racemic form.
Acta Chemica Scandinavica, B31, 671-678 (1977) discloses a number of 5,6-dihydro-2-pyranones including the 6-(2-phenylethyl) compound of formula 3a in Table 1.